Within the framework of the NCI-sponsored Cohort Consortium, investigators from 12 prospective epidemiologic cohorts formed the Pancreatic Cancer Cohort Consortium in 2006. The groups study, also known as PanScan, is funded by the National Cancer Institute (NCI) and involves a genome-wide association study (GWAS) of common genetic variants to identify markers of susceptibility to pancreatic cancer. In 2007, the study was expanded to include 8 case-control studies. The study team includes scientists from the cohorts comprising the Consortium and NCI. PanScan 1 and 2 were conducted in 12 cohort studies and 8 case-control studies, leading to the discovery of four novel regions in the genome associated with risk for pancreatic adenocarcinoma. We an ongoing third phase of PanScan to conduct a new GWAS of 1,600 recently identified incident pancreatic cancer cases with an equal number of controls drawn from 19 cohorts from the cohort consortium, including the 12 prospective cohorts who participated in PanScan 1 and 2, and seven newly joined cohorts. Our study will include approximately 1600 new incident pancreatic cancer cases with consent and acceptable quality DNA to be part of the study. We will also be using and/or genotyping data from controls without previous pancreatic cancer that were part of previous GWAS studies. Specifically, we will analyze a dense set of common genetic variants in the human genome, single nucleotide polymorphisms (SNPs) with minor allele frequencies 5%. The panel of SNPs is based on an analysis of common SNPs in individuals of northern European background determined by the International HapMap Project and provides an opportunity to monitor tested and untested SNPs because of linkage disequilibrium in the genome. The current panel of markers for the GWAS includes 610,000 SNPs, and it is estimated that these serve as markers for approximately 90% of all common SNPs in Europeans and East Asians.A joint analysis of the newly scanned cases will be conducted with cases from PanScan1 and 2 to identify novel regions of the genome associated with pancreatic cancer susceptibility. We will also conduct a GWAS analysis of pancreatic cancer survival using cases from both the cohorts and case-control studies. With the larger sample size (5,500 cases and 13,500 controls), we anticipate that we will identify new genetic risk variants for etiology and perhaps survival. It is notable that our study will include 3,200 incident cases from the cohort consortium, which are more likely to represent the diversity of pancreatic cancers at presentation. In order to accelerate the pace of discovery and characterization of genetic markers associated with pancreatic cancer risk, the genotype results and executive summaries of individual SNP analyses will be posted on a controlled-access web site, available to the biomedical research community in accord with NIH policy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIACP010193-07
Application #
8763639
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$468,522
Indirect Cost
Name
Division of Cancer Epidemiology and Genetics
Department
Type
DUNS #
City
State
Country
Zip Code
Wolpin, Brian M; Rizzato, Cosmeri; Kraft, Peter et al. (2014) Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. Nat Genet 46:994-1000
Jia, Jinping; Bosley, Allen D; Thompson, Abbey et al. (2014) CLPTM1L promotes growth and enhances aneuploidy in pancreatic cancer cells. Cancer Res 74:2785-95
Petersen, Gloria M; Amundadottir, Laufey; Fuchs, Charles S et al. (2010) A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet 42:224-8